Streptococcus pyogenes (S. pyogenes) is a Gram-positive beta-hemolytic bacterium classified in Lancefield serogroup A (commonly known as group A streptococci). S. pyogenes is the cause of many important human diseases, ranging from mild superficial throat (e.g., pharyngitis) and skin infections (e.g., impetigo) to life-threatening systemic diseases. Infections typically begin in the throat or skin. S. pyogenes is the most common bacterial cause of acute pharyngitis in children (15-30% of pediatric cases) and adults (5-10% of adult cases). The economic burden for treating pharyngitis is substantial. The medical costs associated with just treating pharyngitis in children in the United States alone reaches an estimated 540 million dollars per year. In addition to being a common etiological agent of upper respiratory tract and skin infections, S. pyogenes also causes certain invasive systemic infections. Nevertheless, asymptomatic infection and carriage are also common features of S. pyogenes infection.
Importantly, S. pyogenes is an infrequent but usually pathogenic part of skin flora in humans that is responsible for, or implicated in, a wide variety of diseases and morbidities. These diseases are generally referred to as Group A Streptococcal (GAS) diseases. GAS diseases include a diverse variety of suppurative aliments and nonsuppurative postinfectious sequelae. Suppurative GAS diseases are known to include pharyngitis (e.g., tonsillopharyngeal cellulitis or abscess), impetigo, pneumonia, necrotizing fasciitis, cellulitis, Streptococcal bacteremia, osteomyelitis, otitis media, scarlet fever, sinusitis, and even meningitis or brain abscess can occur as sever but fortunately rare complications of ear or sinus infections. In turn, nonsuppurative sequelae of GAS infections include acute rheumatic fever (ARF) (as defined by the Jones criteria), rheumatic heart disease, and acute glomerulonephritis. S. pyogenes is also a known cause of toxic shock syndrome (TSS).
Military units have long recognized the importance of S. pyogenes infections and of GAS disease as major burdens on unit readiness and effectiveness. S. pyogenes was one of the first pathogens specifically identified as a causative bacterial agent of considerable morbidity in massed troops. During World War II, scarlet fever, a GAS disease, was responsible for more than 1.3 million lost workdays in the United States Army. More than 1,600 cases of recognized streptococcal illness were documented for every 108 cases of malaria and one (1) case of polio. The highest incidence of streptococcal illness was among recruits. Unlike malaria and polio, in which symptomatic individuals would likely seek medical attention, infected recruits typically failed to report their illness or to seek medical attention further exacerbating the spread of GAS disease related issues within military units.
A number of factors make prevention of S. pyogenes caused illness difficult, in both the military and civilian populations, these factors include, asymptomatic carriage of S. pyogenes, prolonged bacterial shedding following symptomatic illness, and the potential for direct transmission to uninfected individuals. A vaccine for the prevention of S. pyogenes infection would be beneficial not only for the military but would also have a tremendous impact on improving health in civilian populations.
In the United States, there are an estimated 10 million cases of non-invasive GAS disease and between 9,000-11,500 cases of invasive disease annually. (hypertext transfer protocol://www.cdc.gov/ncidod/dbmd/diseaseinfo/groupastreptococcal_t.htm). GAS Disease resulting from invasive infection can have mortality rates as high as 35%. Indeed, an estimated 500,000 deaths worldwide are attributed to S. pyogenes infections each year. (hypertext transfer protocol://www.who.int/child_adolescent health/documents/ivb_05_14/en/, 2005). Although the overall incidence of total GAS disease related deaths are low, the mortality rate among cases of streptococcal toxic shock-like syndrome is relatively high at about 45%. Additionally, there is growing evidence for the role of GAS infection in the causation of pediatric autoimmune neuropsychiatric disorders (PANDAS).
While GAS infections can generally be successfully treated with antibiotics these treatments cannot guarantee prevention of complications (e.g., pediatric glomerulonephritis) associated with the underlying infection. Reliance on the use of antibiotics can result in antibiotic resistant strains arising in a population. Indeed, antibiotic resistant strains of S. pyogenes have recently emerged and have thusly become an additional concern in combating GAS diseases.
Due to the wide range of morbidities associated with S. pyogenes infection, the potential for outbreaks of antibiotic resistant S. pyogenes infections, and the correspondingly high medical costs for treating GAS infections as well as the lost productivity and, more importantly, potential for human deaths sometimes resulting from GAS diseases an effective vaccine against S. pyogenes is needed both in the ranks of the military as well as in civilian populations. An effective vaccine could save thousands of lives and allow for billions of dollars of medical expenditures to be saved by reducing the number of S. pyogenes infection and/or GAS associated diseases.